Serum HBcrAg Profiles in Chronic Hepatitis B Patients Treated With First-Line Oral Antiviral Therapy

Abstract

Background: Serum hepatitis B core-related antigen (HBcrAg) is a potential surrogate marker for intra-hepatic covalently-closed circular DNA in chronic hepatitis B (CHB) . We aimed to study the profiles of serum HBcrAg in CHB patients treated with first-line oral nucleos(t)ide analogues (NA): entecavir (ETV), tenofovir disoproxil fumarate (TDF) or tenofovir alafenamide (TAF) . Methods: Serum HBcrAg was measured in 264 NA-treated CHB patients (ETV: TDF: TAF = 197: 30: 37) using the Lumipulse G HBcrAg assay in a Lumipulse G1200 analyzer (Fujirebio Inc, Toyko, Japan) with a lower detection limit of 100 units per milliliter (U/ml) . The values of HBcrAg were log transformed and were expressed in log U/mL . Serum HBcrAg levels were measured at baseline, 48-week and 96-week of NA therapy . Results: Among the 264 patients, 130 (49 .2%) were hepatitis B e antigen (HBeAg) positive . In this interim report, HBcrAg level measurements were completed for all 3 groups of patients at baseline and week 48 and for TDF and TAF treated patients at week 96 . All 3 first-line NAs led to significant decline of serum HBcrAg at 48-week compared to baseline (ETV: 1.97 vs. 3.02, TDF: 2.88 vs. 4.49, and TAF: 3.00 vs. 4.36, respectively; all p <0.001). For TDF and TAF, further decline of HBcrAg was observed at 96-week compared to 48-week (TDF: 2.09 vs. 2.88, and TAF 1.89 vs. 3.00, respectively; both p<0.01) [figure]. However, when only HBeAg-negative patients were analyzed, the drop in HBcrAg at 96-week compared to 48-week was not significant for both TDF and TAF treated patients (0.62 vs. 1.08 and 0.56 vs. 0.80, respectively; both p>0.05). There were no significant differences for the magnitude of HBcrAg decline at 48-week between the 3 different types of NAs (ETV: 1.088; TDF: 1.437; TAF: 1.318; p>0.05 for all 3 comparisons). Similarly, TDF and TAF produced no significant differences in the magnitude of HBcrAg decline at 96-week (2 .20 vs . 1 .74, p>0.05). Conclusion: The 3 first-line NAs showed similar potencies in suppression of viral activity upon 1 year duration of therapy. The lack of significant drop of HBcrAg in HBeAgnegative patients reflects the limited utility of this marker in HBeAg-negative phase. [https://doi.org/10.1002/hep.30941 ]